A Review of the Literature on End-of-life Care: Setting a Research Agenda for Maine

In 2002, Last Acts, a national campaign of the Robert Wood Johnson Foundation, issued a report assessing the states on access to end-of-life care and policies supporting its provision. Quite striking for the hospice providers and other stakeholders of Maine, the state ranked second to last in hospice use among persons over age 65 in their last year of life. Although anecdotal and unpublished data suggest that hospice use is on the rise in Maine, concerns about the low use rate remains a concern to those interested in end-of-life care in the State. In order to better understand the factors influencing the use of hospice in Maine, the Maine Hospice Council asked the Muskie School of Public Service to conduct a literature review synthesizing current knowledge on outcomes, use, cost, and barriers to end-of-life care. This review provides a foundation for setting an overall research agenda for the Council. At the end of the report, we have outlined a set of questions for further research regarding end-of-life care in Maine

There's No Place Like Home: Crown-of-Thorns Outbreaks in the Central Pacific Are Regionally Derived and Independent Events

One of the most significant biological disturbances on a tropical coral reef is a population outbreak of the fecund, corallivorous crown-of-thorns sea star, Acanthaster planci. Although the factors that trigger an initial outbreak may vary, successive outbreaks within and across regions are assumed to spread via the planktonic larvae released from a primary outbreak. This secondary outbreak hypothesis is predominantly based on the high dispersal potential of A. planci and the assertion that outbreak populations (a rogue subset of the larger population) are genetically more similar to each other than they are to low-density non-outbreak populations. Here we use molecular techniques to evaluate the spatial scale at which A. planci outbreaks can propagate via larval dispersal in the central Pacific Ocean by inferring the location and severity of gene flow restrictions from the analysis of mtDNA control region sequence (656 specimens, 17 non-outbreak and six outbreak locations, six archipelagos, and three regions). Substantial regional, archipelagic, and subarchipelagic-scale genetic structuring of A. planci populations indicate that larvae rarely realize their dispersal potential and outbreaks in the central Pacific do not spread across the expanses of open ocean. On a finer scale, genetic partitioning was detected within two of three islands with multiple sampling sites. The finest spatial structure was detected at Pearl & Hermes Atoll, between the lagoon and forereef habitats (<10 km). Despite using a genetic marker capable of revealing subtle partitioning, we found no evidence that outbreaks were a rogue genetic subset of a greater population. Overall, outbreaks that occur at similar times across population partitions are genetically independent and likely due to nutrient inputs and similar climatic and ecological conditions that conspire to fuel plankton blooms

Mechanisms of adverse effects of anti-VEGF therapy for cancer

Advances in understanding the role of vascular endothelial growth factor (VEGF) in normal physiology are giving insight into the basis of adverse effects attributed to the use of VEGF inhibitors in clinical oncology. These effects are typically downstream consequences of suppression of cellular signalling pathways important in the regulation and maintenance of the microvasculature. Downregulation of these pathways in normal organs can lead to vascular disturbances and even regression of blood vessels, which could be intensified by concurrent pathological conditions. These changes are generally manageable and pose less risk than the tumours being treated, but they highlight the properties shared by tumour vessels and the vasculature of normal organs

Recommendations for measuring whisker movements and locomotion in mice with sensory, motor and cognitive deficits.

BACKGROUND: Previous studies have measured whisker movements and locomotion to characterise mouse models of neurodegenerative disease. However, these studies have always been completed in isolation, and do not involve standardized procedures for comparisons across multiple mouse models and background strains. NEW METHOD: We present a standard method for conducting whisker movement and locomotion studies, by carrying out qualitative scoring and quantitative measurement of whisker movements from high-speed video footage of mouse models of Amyotrophic Lateral Sclerosis, Huntington's disease, Parkinson's disease, Alzheimer's disease, Cerebellar Ataxia, Somatosensory Cortex Development and Ischemic stroke. RESULTS: Sex, background strain, source breeder and genotype all affected whisker movements. All mouse models, apart from Parkinson's disease, revealed differences in whisker movements during locomotion. R6/2 CAG250 Huntington's disease mice had the strongest behavioural phenotype. Robo3R3-5-CKO and RIM-DKOSert mouse models have abnormal somatosensory cortex development and revealed significant changes in whisker movements during object exploration. COMPARISON WITH EXISTING METHOD(S): Our results have good agreement with past studies, which indicates the robustness and reliability of measuring whisking. We recommend that differences in whisker movements of mice with motor deficits can be captured in open field arenas, but that mice with impairments to sensory or cognitive functioning should also be filmed investigating objects. Scoring clips qualitatively before tracking will help to structure later analyses. CONCLUSIONS: Studying whisker movements provides a quantitative measure of sensing, motor control and exploration. However, the effect of background strain, sex and age on whisker movements needs to be better understood

Correction of anaemia through the use of darbepoetin alfa improves chemotherapeutic outcome in a murine model of Lewis lung carcinoma

Darbepoetin alfa (Aranesp®, Amgen) is a novel erythropoiesis-stimulating protein with a serum half-life longer than recombinant human erythropoietin (Epo), used in the treatment of cancer-associated anaemia. Anaemia is known to adversely affect prognosis and response to treatment in cancer patients. Solid tumours contain regions of hypoxia due to poor vascular supply and cellular compaction. Although hypoxic stress usually results in cell death, hypoxia-resistant tumour cells are genetically unstable and often acquire a drug-resistant phenotype. Increasing tumour oxygenation and perfusion during treatment could have the doubly beneficial outcome of reducing the fraction of treatment-resistant cells, while increasing drug delivery to previously hypoxic tissue. In this study, we examined the effect of darbepoetin alfa on chemotherapy sensitivity and delivery in an in vivo model of Lewis lung carcinoma, shown here to express the Epo receptor (EpoR). We identified that weekly darbepoetin alfa treatment, commencing 10 days before chemotherapy, resulted in a significant reduction in tumour volume compared to chemotherapy alone. This was mediated by the prevention of anaemia, a reduction in tumour hypoxia and a concomitant increase in drug delivery. Darbepoetin alfa treatment alone did not modulate the growth of the EpoR-expressing tumour cells. This study identifies an important role for darbepoetin alfa in increasing the therapeutic index of chemotherapy

“Microbiota, symbiosis and individuality summer school” meeting report

How does microbiota research impact our understanding of biological individuality? We summarize the interdisciplinary summer school on “Microbiota, symbiosis and individuality: conceptual and philosophical issues” (July 2019), which was supported by a European Research Council starting grant project “Immunity, DEvelopment, and the Microbiota” (IDEM). The summer school centered around interdisciplinary group work on four facets of microbiota research: holobionts, individuality, causation, and human health. The conceptual discussion of cutting-edge empirical research provided new insights into microbiota and highlights the value of incorporating into meetings experts from other disciplines, such as philosophy and history of science

High Connectivity in the Deepwater Snapper Pristipomoides filamentosus (Lutjanidae) across the Indo-Pacific with Isolation of the Hawaiian Archipelago

In the tropical Indo-Pacific, most phylogeographic studies have focused on the shallow-water taxa that inhabit reefs to approximately 30 m depth. Little is known about the large predatory fishes, primarily snappers (subfamily Etelinae) and groupers (subfamily Epinephelinae) that occur at 100–400 m. These long-lived, slow-growing species support fisheries across the Indo-Pacific, yet no comprehensive genetic surveys within this group have been conducted. Here we contribute the first range-wide survey of a deepwater Indo-Pacific snapper, Pristipomoides filamentosus, with special focus on Hawai'i. We applied mtDNA cytochrome b and 11 microsatellite loci to 26 samples (N = 1,222) collected across 17,000 km from Hawai'i to the western Indian Ocean. Results indicate that P. filamentosus is a highly dispersive species with low but significant population structure (mtDNA ΦST = 0.029, microsatellite FST = 0.029) due entirely to the isolation of Hawai'i. No population structure was detected across 14,000 km of the Indo-Pacific from Tonga in the Central Pacific to the Seychelles in the western Indian Ocean, a pattern rarely observed in reef species. Despite a long pelagic phase (60–180 days), interisland dispersal as adults, and extensive gene flow across the Indo-Pacific, P. filamentosus is unable to maintain population connectivity with Hawai'i. Coalescent analyses indicate that P. filamentosus may have colonized Hawai'i 26 K–52 K y ago against prevailing currents, with dispersal away from Hawai'i dominating migration estimates. P. filamentosus harbors low genetic diversity in Hawai'i, a common pattern in marine fishes, and our data indicate a single archipelago-wide stock. However, like the Hawaiian Grouper, Hyporthodus quernus, this snapper had several significant pairwise comparisons (FST) clustered around the middle of the archipelago (St. Rogatien, Brooks Banks, Gardner) indicating that this region may be isolated or (more likely) receives input from Johnston Atoll to the south

The many faces of biological individuality

Biological individuality is a major topic of discussion in biology and philosophy of biology. Recently, several objections have been raised against traditional accounts of biological individuality, including the objections of monism (the tendency to focus on a single individuality criterion and/or a single biological field), theory-centrism (the tendency to discuss only theory-based individuation), ahistoricity (the tendency to neglect what biologists of the past and historians of biology have said about biological individuality), disciplinary isolationism (the tendency to isolate biological individuality from other scientific and philosophical domains that have investigated individuality), and the multiplication of conceptual uncertainties (the lack of a precise definition of “biological individual” and related terms). In this introduction, I will examine the current philosophical landscape about biological individuality, and show how the contributions gathered in this special issue address these five objections. Overall, the aim of this issue is to offer a more diverse, unifying, and scientifically informed conception of what a biological individual is